Environmental Pollutant Polybrominated Diphenyl Ether, a Flame Retardant, Induces Primary Amnion Cell Senescence
Environmental Pollutant Polybrominated Diphenyl Ether, a Flame Retardant, Induces Primary Amnion Cell Senescence
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DOI：
10.1111/aji.12414
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发表时间：
2015-11-01
影响因子：
3.6
通讯作者：
Menon, Ramkumar
中科院分区：
文献类型：
--
作者：
Behnia, Faranak;Peltier, Morgan R.;Menon, Ramkumar
多溴联苯醚（PBDEs）被证明会增加自发性早产的风险。我们假设，多溴联苯醚导致氧化应激（OS），导致胎儿细胞衰老和炎症与PTB.MethodsPrimary羊膜上皮细胞（n = 5）分离的术语，而不是在劳动妊娠，暴露于多溴联苯醚同系物47和99（每个5 μ M）。监测ROS动力学。形态学变化，磷酸-p38 MAPK（P-p38）激活，衰老的发展，并诱导uterotonins（考克斯-2的表达）进行了定量使用光学显微镜，蛋白质印迹，衰老相关的β-半乳糖苷酶（SA β-gal）染色，和qRT-PCR，分别在48和72小时的曝光后。PBDE-99处理后，P-p38活性显著高于对照组（P < 0.05）。经过72小时的处理，两个多溴二苯醚处理的细胞显示出细胞死亡相关的形态学变化，SA β-半乳糖染色的细胞明显高于对照组。用PBDE-99处理72小时后，考克斯-2表达更高。结论PBDE-99可诱导人羊膜细胞发生同源物依赖性OS反应、p38 MAPK激活、衰老和考克斯-2表达。这些发现表明环境污染物诱导的衰老激活和炎症可导致导致PTB的途径。
ObjectivePolybrominated diphenyl ethers (PBDEs) are documented to increase the risk for spontaneous preterm birth (PTB). We hypothesize that PBDEs cause oxidative stress (OS) that leads to fetal cell senescence and inflammation associated with PTB.MethodsPrimary amnion epithelial cells (n = 5) isolated from term, not in labor pregnancies, were exposed to PBDE congeners 47 and 99 (each 5 mu M). ROS kinetics was monitored. Morphologic changes, phospho-p38 MAPK (P-p38) activation, development of senescence, and induction of uterotonins (COX-2 expression) were quantified using light microscopy, Western blot, senescence-associated beta-galactosidase (SA beta-gal) staining, and qRT-PCR, respectively, after 48 and 72 hr of exposure.ResultsBoth PBDE congeners induced ROS within 2 min compared to controls (P < 0.05). P-p38 activation was significant after PBDE-99 treatment than controls (P < 0.05). After 72 hr of treatment, both PBDE-treated cells showed cell death-associated morphologic changes with significantly higher SA beta-gal-stained cells than control. COX-2 expression was higher after 72 hr of treatment with PBDE-99. Overall, the PBDE-99 response was more pronounced than PBDE-47.ConclusionsCongener-dependent OS response, p38 MAPK activation, senescence, and COX-2 expression were seen in human amnion cells by PBDEs. These findings demonstrate environment pollutant-induced senescence activation and inflammation can lead to pathways resulting in PTB.